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1.
Oncology ; : 1-8, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32454480

RESUMO

BACKGROUND: Anthracycline is used to treat various types of cancer; however, cardiotoxicity negatively affects patient prognosis. OBJECTIVES: The aim of the present study was to investigate serial changes in levels of cardiac troponin I (TnI) and B-type natriuretic peptide (BNP) in patients treated with anthracycline-containing therapy. METHODS: 91 consecutive cancer patients planned for anthracycline treatment were enrolled and followed up for 12 months. All patients underwent echocardiography and blood sampling at baseline, 3, 6, and 12 months. RESULTS: The patients were divided into two groups based on their TnI level during the follow-up period: the elevated TnI group (TnI ≥0.03 ng/mL; n = 37) and the normal TnI group (n = 54). In the elevated TnI group, the TnI levels increased at 3 and 6 months, but they returned to within normal range at 12 months after anthracycline administration. Unlike TnI, the BNP levels began to increase after 6 months, and remained increased at 12 months. The occurrence of cancer therapeutics-related cardiac dysfunction was higher in the elevated TnI group than in the normal TnI group. When we set the cut-off value of TnI at 0.029 ng/mL, sensitivity and specificity to predict an elevated BNP level of more than 100 pg/mL were 90 and 63%, respectively. Multivariate logistic regression analysis revealed that elevated TnI was an independent predictor of elevated BNP levels. CONCLUSION: Elevated TnI was an independent predictor for the development of BNP increase. The different characteristics of TnI and BNP should be considered when managing patients treated with anthracycline-containing therapy.

2.
Sci Rep ; 10(1): 6872, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32327716

RESUMO

People in the Solomon Islands today are considered to have derived from Asian- and Papuan-related ancestors. Papuan-related ancestors colonized Near Oceania about 47,000 years ago, and Asian-related ancestors were Austronesian (AN)-speaking population, called Lapita, who migrated from Southeast Asia about 3,500 years ago. These two ancestral populations admixed in Near Oceania before the expansion of Lapita people into Remote Oceania. To understand the impact of the admixture on the adaptation of AN-speaking Melanesians in Near Oceania, we performed the genome-wide single nucleotide polymorphism (SNP) analysis of 21 individuals from Munda, the main town of the New Georgia Islands in the western Solomon Islands. Population samples from Munda were genetically similar to other Solomon Island population samples. The analysis of genetic contribution from the two different ancestries to the Munda genome revealed significantly higher proportions of Asian- and Papuan-related ancestries in the region containing the annexin A1 (ANXA1) gene (Asian component > 82.6%) and in the human leukocyte antigen (HLA) class II region (Papuan component > 85.4%), respectively. These regions were suspected to have undergone natural selection since the time of admixture. Our results suggest that admixture had affected adaptation of AN-speaking Melanesians in the Solomon Islands.

3.
BMC Complement Med Ther ; 20(1): 118, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32306956

RESUMO

BACKGROUND: Lubiprostone (LBP) is a novel chloride channel opener that has been reported to activate chloride channel protein 2 (ClC-2) and cystic fibrosis transmembrane conductance regulator (CFTR). LBP facilitates fluid secretion by activating CFTR in the intestine and is used as a drug for treating chronic constipation. While ClC-2 and CFTR expression has been confirmed in cardiomyocytes (CMs), the effect of LBP on CMs has not yet been investigated. Thus, the present study aimed to investigate the effect of LBP on CMs using mouse-induced pluripotent stem (iPS) cell-derived CMs (iPS-CMs). METHODS: We induced mouse iPS cells into CMs through embryoid body (EB) formation. We compared the differentiated cells to CMs isolated from adult and fetal mice using gene expression, spontaneous beating rate, and contraction ratio analyses. RESULTS: Gene expression analysis revealed that, in the iPS-CMs, the mRNA expression of the undifferentiated cell markers Rex1 and Nanog decreased, whereas the expression of the unique cardiomyocyte markers cardiac troponin I (cTnI) and cardiac troponin T (cTNT), increased. Immunostaining showed that the localization of cTnI and connexin-43 in the iPS-CMs was similar to that in the primary fetal CMs (FCMs) and adult CMs (ACMs). LBP decreased the spontaneous beating rate of the iPS-CMs and FCMs, and decreased the contraction ratio of the iPS-CMs and ACMs. The reduction in the beating rate and contraction ratio caused by LBP was inhibited by glycine hydrazide (GlyH), which is a CFTR inhibitor. CONCLUSION: These results suggest that LBP stimulates CFTR in CMs and that LBP has negative chronotropic and inotropic effects on CMs. LBP may be useful for treating cardiac diseases such as heart failure, ischemia, and arrhythmia.

4.
Int Heart J ; 61(2): 301-307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224602

RESUMO

Pulmonary hypertension (PH) caused by left-sided heart disease (LHD-PH) is classified into 2 types: isolated post-capillary PH (Ipc-PH) and combined pre- and post-capillary PH (Cpc-PH). However, the impact of pulmonary vascular resistance (PVR) or diastolic pressure gradient (DPG) on the prognosis of LHD-PH has varied among previous studies. Thus, we verified the significance of PVR or DPG on the prognosis of LHD-PH in our series.We analyzed 243 consecutive LHD-PH patients. The patients were divided into 3 groups: Group A, patients with PVR ≤ 3 Wood unit (WU) and DPG < 7 mmHg; Group B, patients with either PVR > 3 WU or DPG ≥ 7 mmHg; and Group C, patients with PVR > 3 WU and DPG ≥ 7 mmHg.The Kaplan-Meier curve demonstrated that Group B had lower cardiac death-free survival compared with Group A, whereas no significant differences were observed when compared with Group C. In the Cox hazard model, DPG was not associated with cardiac death in the LHD-PH patients. However, only in the ischemic heart disease group, patients with DPG ≥ 7 mmHg had worse prognosis compared with those with normal DPG.The cardiac death-free rate of patients with either increased PVR or DPG was close to that of patients with both increased PVR and DPG. It seems reasonable to define Cpc-PH only by PVR in the new criteria. However, the significance of DPG in LHD-PH might be dependent on the underlying cause of LHD-PH.


Assuntos
Pressão Sanguínea/fisiologia , Diástole/fisiologia , Insuficiência Cardíaca/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Taxa de Sobrevida , Resistência Vascular/fisiologia , Adulto , Idoso , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Morte , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Prognóstico , Modelos de Riscos Proporcionais
5.
J Am Heart Assoc ; 9(7): e013982, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32200713

RESUMO

Background The prognostic impact of benzodiazepines has been unclear in patients with heart failure (HF). Methods and Results This was a historical observational cohort study. A total of 826 patients who had been hospitalized for HF and were being treated for insomnia with either benzodiazepines or Z-drugs (zolpidem, zopiclone, or eszopiclone), were enrolled and divided on the basis of their hypnotics: benzodiazepine group (n=488 [59.1%]) and Z group (n=338 [40.9%]). We compared the patient characteristics and postdischarge prognosis between the groups. The primary end points were rehospitalization for HF and cardiac death. The benzodiazepine group was older (age, 72.0 versus 69.0 years; P=0.010), had a higher prevalence of depression (17.4% versus 8.9%; P<0.001), and showed a higher use of loop diuretics (77.9% versus 67.8%; P=0.001). In the laboratory data, the benzodiazepine group demonstrated lower levels of hemoglobin (12.3 versus 13.0 g/dL; P=0.001), sodium (139.0 versus 140.0 mEq/L; P=0.018), and albumin (3.7 versus 3.9 g/dL; P=0.003). Kaplan-Meier analysis showed that both end points were higher in the benzodiazepine group (rehospitalization for HF, log-rank P=0.001; cardiac death, log-rank P=0.043). Multiple Cox proportional hazard analysis revealed that the use of benzodiazepines was an independent predictor of rehospitalization for HF (hazard ratio, 1.530; 95% CI, 1.025-2.284; P=0.038). Furthermore, rehospitalization for HF was higher in the benzodiazepine group after propensity score matching (log-rank P=0.036). Conclusions Benzodiazepine is associated with higher risk of rehospitalization for HF compared with Z-drugs in patients with HF.

6.
Radiology ; 295(2): 439-445, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32154776

RESUMO

Background Although the National Lung Screening Trial reported a significant reduction in lung cancer mortality when low-dose (LD) CT chest examinations are used for a diagnosis, their biologic effects from radiation exposure remain unclear. Purpose To compare LD CT and standard-dose (SD) CT for DNA double-strand breaks and chromosome aberrations (CAs) in peripheral blood lymphocytes. Materials and Methods Between March 2016 and June 2018, 209 participants who were referred to a respiratory surgery department for chest CT studies were prospectively enrolled in this study. Individuals were excluded if they had undergone radiography examinations within the last 3 days or had undergone chemotherapy or radiation therapy. Peripheral blood samples were obtained before and 15 minutes after CT. The number of γ-H2AX foci and unstable CAs in lymphocytes was quantified by immunofluorescent staining of γ-H2AX and by fluorescence in situ hybridization by using peptide nucleic acid probes for centromeres and telomeres, respectively. The Wilcoxon signed rank test was used for statistical analysis. Bonferroni correction was applied for multiple comparisons. Results Of the 209 participants (105 women, 104 men; mean age, 67.0 years ± 11.3 [standard deviation]), 107 underwent chest LD CT and 102 underwent chest SD CT. Sex distribution, age, and body size metrics were similar between the two groups. The median effective dose of LD CT and SD CT was 1.5 and 5.0 mSv, respectively. The number of double-strand breaks and CAs increased after a SD CT examination (γ-H2AX, P < .001; CAs, P = .003); the number of double-strand breaks and CAs before and after LD CT was not different (γ-H2AX, P = .45; CAs, P = .69). Conclusion No effect of low-dose CT on human DNA was detected. In the same setting, DNA double-strand breaks and chromosome aberrations increased after standard-dose CT. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Brenner in this issue.

7.
Ann Noninvasive Electrocardiol ; : e12749, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32083399

RESUMO

BACKGROUND: Cardiac amyloidosis (CA) is characterized by left ventricular hypertrophy (LVH) and autonomic nervous imbalance due to amyloid infiltration. However, autonomic dysfunction is often seen in heart failure (HF) with LVH from other etiologies. We aimed to characterize autonomic dysfunction in CA from other etiologies of LVH. METHODS: Fifty-five HF patients with LVH (35 males, mean age 65 ± 16 years) were enrolled. LVH was defined as left ventricular mass index measured by echocardiography >95 g/m2 in women and 115 g/m2 in men. The etiology was as follows: amyloid light chain (AL)-CA, n = 14; hypertrophic cardiomyopathy, n = 21; and aortic stenosis (AS), n = 20. With the patient in a clinically stable condition, heart rate variability (HRV) and heart rate turbulence (HRT), which reflect autonomic dysfunction, were measured using Holter monitoring and compared among the three groups. RESULTS: Brain natriuretic peptide levels, LVH severity, left ventricular ejection fraction, and tissue Doppler index E/e' did not differ among the three groups. However, severe abnormalities of HRV and HRT were obtained in AL-CA. In the ROC analysis to identify AL-CA in HF with LVH, the best cutoff value for standard deviation of all R-R intervals, standard deviation of the 5-min mean R-R intervals, turbulence onset, and turbulence slope were 68.5 ms (AUC: 0.865), 58.5 ms (AUC: 0.834), 0.25% (AUC: 0.813), and 1.00 ms/RR (AUC 0.736), respectively. CONCLUSION: Autonomic dysfunction is a hallmark of AL-CA, and its noninvasive assessment by Holter monitoring may be a useful tool for differential diagnosis of HF with LVH.

8.
Chromosoma ; 129(1): 57-67, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31925526

RESUMO

In the Cercopithecini ancestor two chromosomes, homologous to human chromosomes 20 and 21, fused to form the Cercopithecini specific 20/21 association. In some individuals from the genus Cercopithecus, this association was shown to be polymorphic for the position of the centromere, suggesting centromere repositioning events. We set out to test this hypothesis by defining the evolutionary history of the 20/21 association in four Cercopithecini species from three different genera. The marker order of the various 20/21 associations was established using molecular cytogenetic techniques, including an array of more than 100 BACs. We discovered that five different forms of the 20/21 association were present in the four studied Cercopithecini species. Remarkably, in the two Cercopithecus species, we found individuals in which one homolog conserved the ancestral condition, but the other homolog was highly rearranged. The phylogenetic analysis showed that the heterozygosity in these two species originated about 8 million years ago and was maintained for this entire arc of time, surviving multiple speciation events. Our report is a remarkable extension of Dobzhansky's pioneering observation in Drosophila concerning the maintenance of chromosomal heterozygosity due to selective advantage. Dobzhansky's hypothesis recently received strong support in a series of detailed reports on the fruit fly genome. Our findings are first extension to primates, indeed to Old World monkeys phylogenetically close to humans of an analogous situation. Our results have important implications for hypotheses on how chromosome rearrangements, selection, and speciation are related.

9.
Asian Pac J Cancer Prev ; 21(1): 243-248, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31983191

RESUMO

BACKGROUND: CYP1A1 is an enzyme in phase I of the cytochrome P450 (CYP) superfamily, and plays a key role in detoxification of carcinogens. Host genetic predisposition in the CYP1A1 may be associated with an increased susceptibility to cervical cancer.The study aimed to evaluate four common polymorphisms of the CYP1A1 and cervical cancer susceptibility among Northeast Thai women. METHODS: A case-control study was conducted involving 204 patients with squamous cell cervical cancer (SCCA) and 204 age-matched healthy controls. DNA was extracted from peripheral blood leucocytes. CYP1A1 m1, m3, and m4 genotypes were detected using PCR-RFLP, whereas the CYP1A1 m2 genotype was investigated using real-time PCR. Haplotype analysis was performed using PHASE algorithm version 2.1.1. RESULTS: CYP1A1 m3 was monomorphic. Association between the common CYP1A1 polymorphisms, m1 and m2, and cervical cancer risk was not observed (p>0.05), nor was any association found between the m1-m2-m4 haplotype and cervical cancer risk (p>0.05). Interestingly, the CA genotype of CYP1A1 m4 was observed in 30.88% of the cervical cancer patients but was absent in healthy controls. CONCLUSION: Our results demonstrated a possible involvement of the CYP1A1 m4 polymorphism but no other common polymorphisms (viz., m1, m2, and m3) in the risk for cervical cancer.This finding may be useful when screening for risk of cervical cancer among Northeast Thai women.
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10.
Intern Med ; 59(2): 221-227, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31511490

RESUMO

Pulmonary hypertension and hereditary hemorrhagic telangiectasia (HHT) have an association mediated by activin A receptor type II-like 1 (ACVRL1) gene pathogenic variants. A 30-year-old woman was previously admitted to a hospital due to lung hemorrhage, and was diagnosed with pulmonary hypertension, but stopped follow-up visits. At 48 years of age, she was admitted to our hospital and was diagnosed with HHT. Genetic testing revealed an ACVRL1 pathogenic variant. After the initiation of pulmonary vasodilator treatment, the patient's mean pulmonary artery pressure started to decrease from 43 mmHg, declining to 37 mmHg when she was 58 years of age. This is the first report describing the 28-year follow-up of an HHT and pulmonary hypertension patient with an ACVRL1 mutation.

11.
BMC Cardiovasc Disord ; 19(1): 298, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847799

RESUMO

BACKGROUND: Patients with some mutations in the lamin A/C (LMNA) gene are characterized by the presence of dilated cardiomyopathy (DCM), conduction abnormalities, ventricular tachyarrhythmias (VT), and sudden cardiac death (SCD). Various clinical features have been observed among patients who have the same LMNA mutation. Here, we show a family with cardiac laminopathy with a c.475G > T, p.E159* LMNA mutation, and a family history of conduction disorder, DCM, VT, and SCD. CASE PRESENTATION: A proband (female) with atrial fibrillation and bradycardia was implanted with a pacemaker in her fifties. Twenty years later, she experienced a loss of consciousness due to polymorphic VT. She had a serious family history; her mother and elder sister died suddenly in their fifties and sixties, respectively, and her nephew and son were diagnosed as having DCM. Genetic screening of the proband, her son, and nephew identified a nonsense mutation (c.475G > T, p.E159*) in the LMNA gene. Although the proband's left ventricular ejection fraction remained relatively preserved, her son and nephew's left ventricular ejection fraction were reduced, resulting in cardiac resynchronization therapy by implantation of a defibrillator. CONCLUSIONS: In this family with cardiac laminopathy with a c.475G > T, p.E159* LMNA mutation, DCM, SCD, and malignant VT occurred. Clinical manifestation of various atrial and ventricular arrhythmias and heart failure with reduced ejection fraction occurred in an age-dependent manner in all family members who had the nonsense mutation. It appears highly likely that the E159* LMNA mutation is related to various cardiac problems in the family of the current report.

12.
Int Heart J ; 60(6): 1441-1443, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666456

RESUMO

Hereditary ATTR amyloid cardiomyopathy is defined as the intramyocardial deposition of amyloid fibrils derived from the mutation of transthyretin (TTR). A 51-year-old man was referred to our hospital for congestive heart failure. He and his family had no past history of heart diseases. Echocardiography showed remarkable left ventricular hypertrophy and reduced ejection fraction. Endomyocardial biopsy specimens presented positive staining of Congo-Red and transthyretin. A genetic test showed heterozygous V122I TTR gene mutation, which is very rare in Japan. We diagnosed him as with sporadic ATTR amyloidosis with mutation, and tafamidis was administered to stabilize TTR tetramer. Since the phenotype of ATTR amyloidosis varies depending on its penetration rate, it is crucial to always keep in mind the possibility of hereditary ATTR amyloidosis even in the case of amyloidosis with no clear family history.


Assuntos
Neuropatias Amiloides Familiares/diagnóstico , Cardiomiopatias/etiologia , Mutação/genética , Pré-Albumina/genética , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/genética , Humanos , Masculino , Pessoa de Meia-Idade
13.
Int Heart J ; 60(6): 1430-1434, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31735783

RESUMO

Pulmonary arterial hypertension is a fatal disease caused by pulmonary arterial vasoconstriction and organic stenosis due to the proliferation of pulmonary smooth muscle cells and endothelial cells. Endothelial dysfunction, including impaired nitric oxide (NO) bioavailability, plays a crucial role in the pathogenesis of pulmonary hypertension, and endothelial nitric oxide synthase (eNOS) is an important modulator of pulmonary vasodilatation. Although senescence marker protein (SMP) 30 is known as an anti-aging protein, the role of SMP30 in pulmonary vessels is still unclear. In this study, we examined the role of SMP30 in pulmonary vasculature using SMP30-deficient mice.We used female SMP30-deficient mice and wild-type littermate (WT) mice at the age of 12 to 18 weeks. The WT and SMP30-deficient mice were exposed to normoxia or hypoxia (10% oxygen for 4 weeks). In normoxia, the right ventricular systolic pressure (RVSP) was not different between the WT and SMP30-deficient mice, but in hypoxia, the RVSP was significantly higher in the SMP30-deficient mice compared to the WT mice (P < 0.05). The hypoxia-induced increases in right ventricular hypertrophy and medial smooth muscle area of the pulmonary artery were comparable between the WT and the SMP30-deficient mice. Western blotting showed that eNOS phosphorylation in lung tissue was reduced in the SMP30-deficient mice compared to the WT mice in normoxia. However, in hypoxic conditions, eNOS phosphorylation was reduced in both the WT and SMP30-deficient mice with no differences in Akt phosphorylation.Our study demonstrated that SMP30 is involved in the development of hypoxia-induced pulmonary hypertension by impairment of eNOS activity.


Assuntos
Proteínas de Ligação ao Cálcio/fisiologia , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/metabolismo
14.
Int Heart J ; 60(5): 1147-1153, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484872

RESUMO

Heart failure causes increased venous pressure, leading to liver dysfunction. The fibrosis-4 index is a simple index for liver fibrosis and has been reported to be useful for predicting prognosis in heart failure; however, its impact on patients with pulmonary hypertension due to left heart disease (PH-LHD) has not yet been fully elucidated.We enrolled consecutive 230 hospitalized patients who had been diagnosed as having PH-LHD. The fibrosis-4 index was calculated as follows: [aspartate transaminase (U/L) × age]/[alanine transaminase 1/2 (U/L) × platelet count (109/L) ]. We followed patients for all-cause mortality during the follow-up period (mean 1112 ± 822 days).The patients were divided into tertiles based on their fibrosis-4 index: the first tertile 0.335 to 1.381; the second tertile 1.391 to 2.311; and the third tertile 2.323 to 14.339. Compared with the first tertile, the third tertile had lower estimated glomerular filtration rates and hemoglobin levels. All-cause mortality was significantly higher in the third than in the first tertile. In a Cox proportional hazard model, the fibrosis-4 index was a predictor of all-cause mortality in PH-LHD patients (HR 1.212, 95% CI 1.099-1.337, P < 0.001).The fibrosis-4 index is associated with kidney function, anemia, and high mortality in PH-LHD patients.


Assuntos
Causas de Morte , Insuficiência Cardíaca/mortalidade , Hipertensão Pulmonar/mortalidade , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/patologia , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Fibrose/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Hospitais Universitários , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Análise de Sobrevida , Disfunção Ventricular Esquerda/sangue
15.
Circ J ; 83(8): 1709-1717, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31243245

RESUMO

BACKGROUND: Heart failure (HF) and cancer (CA) are becoming increasingly prevalent as the population ages. We aimed to evaluate prior history and occurrence of CA and its prognostic impact on HF.Methods and Results:Consecutive hospitalized HF patients (n=2,103) were divided into 2 groups according to prior history of CA: non-prior-CA group (n=1,828) and prior-CA group (n=275). Compared with the non-prior-CA group, the prior-CA group were older, and had higher prevalence of chronic kidney disease, anemia, and atrial fibrillation (P<0.05). In contrast, sex, other comorbidities, levels of natriuretic peptide and ejection fraction were comparable between groups. We focused on newly diagnosed CA after discharge for HF. In the follow-up period (median 623 days), 114 (6.2%) patients in the non-prior-CA and 17 (6.2%) patients in the prior-CA groups were newly diagnosed as having CA. Additionally, 83 (3.9%) CA-related patient deaths occurred (median 776 days). In the Kaplan-Meier analysis (median 1,037 days), not only all-cause death but also cardiac event rate was significantly higher in the prior-CA group than in the non-prior-CA group (log-rank P<0.01). In the Cox proportional hazard analysis, CA history was a predictor of cardiac event rate (HR 1.450, 95% CI 1.134-1.822), as well as all-cause death (HR 2.483, 95% CI 2.034-3.030). CONCLUSIONS: Prior-CA history was associated with high cardiac event and mortality rates. CA is notable comorbidity in HF patients.

16.
Int Heart J ; 60(3): 736-745, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31105157

RESUMO

Aging is not only a major risk factor for impaired collateral growth under ischemia but also shortens the telomere length, which is regulated by telomerase. We examined the role of telomerase activity during impaired collateral growth during aging in ischemic skeletal muscle. Unilateral hind limb ischemia was generated in old, young, and old mice chronically administered a telomerase activator. In old mice, blood flow recovery and capillary density development in ischemic hind limbs were reduced compared to those in young mice, and these changes were restored to equal levels by administration of TA-65, a telomerase activator. During the early phase of ischemic muscle changes in old mice, telomerase reverse transcriptase expression and telomerase activity were both low compared to those in young mice and old mice treated with TA-65. Levels of reactive oxygen species (ROS), DNA double-strand breaks, and expression of p53, p16, and Bax/Bcl-2 were all elevated in ischemic muscles of old mice compared to those in the muscles of young mice and old mice treated with TA-65 treatment; these factors were maintained at low levels equivalent to those seen in young mice during the experiment. Expression of HIF1α/vascular endothelial growth factor (VEGF) and PGC1α were decreased in old mice compared to those in young mice and old mice treated with TA-65. Collateral growth under ischemic conditions is impaired in aged animals due to low telomerase activity, increased ROS, resultant DNA damage, and expression of tumor suppressor and pro-apoptotic proteins. These data suggest that telomerase activation enhances collateral growth and rescues ischemic tissue in old individuals.


Assuntos
Envelhecimento/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Isquemia/metabolismo , Telomerase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica , Membro Posterior/irrigação sanguínea , Isquemia/induzido quimicamente , Camundongos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Fluxo Sanguíneo Regional
17.
BMC Cardiovasc Disord ; 19(1): 79, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940076

RESUMO

BACKGROUND: Takayasu arteritis is a rare systemic vasculitis, which affects the aorta and its major branches, especially in young females. Diagnosis and treatment for Takayasu arteritis with coronary stenosis are important to prevent fatal complications. Immunosuppressive treatment such as corticosteroid is a common treatment for this condition. However, the effects of immunosuppressive treatment on inflammatory coronary stenosis caused by Takayasu arteritis remains unknown. CASE PRESENTATION: An 18-year-old female had chest oppression on effort and was referred to our hospital due to ST-segment depression in I, aVL, and V2-4 on electrocardiogram. Coronary angiography showed severe stenosis in the ostium of both the left main trunk and the right coronary artery. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed isolated inflammation of the aortic root. She was diagnosed with Takayasu arteritis and treated with combined immunosuppressive treatment with corticosteroid and tocilizumab, which decreased the FDG uptake in the aortic root. Four months after initiation of the immunosuppressive treatment, coronary angiography showed regression of the coronary ostial stenosis. Coronary artery bypass surgery was considered, but the patient rejected invasive revascularization for coronary artery disease. She did not have chest oppression or ST-segment depression after the immunosuppressive treatment. She had no cardiac events for 6 months after discharge. CONCLUSIONS: We described regressed coronary ostial stenosis in a young female patient with Takayasu arteritis. Immunosuppressive treatment might have a favorable effect on coronary ostial stenosis in Takayasu arteritis.


Assuntos
Corticosteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Estenose Coronária/tratamento farmacológico , Imunossupressores/uso terapêutico , Prednisolona/uso terapêutico , Arterite de Takayasu/tratamento farmacológico , Adolescente , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/etiologia , Quimioterapia Combinada , Feminino , Humanos , Indução de Remissão , Arterite de Takayasu/complicações , Arterite de Takayasu/diagnóstico , Resultado do Tratamento
18.
Intern Med ; 58(15): 2139-2144, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30996169

RESUMO

Objective Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease that leads to right-sided heart failure with electrocardiographic abnormalities. There are only a few reports about the effects of balloon pulmonary angioplasty for CTEPH on the electrocardiographic criteria of right ventricular hypertrophy. To determine the effect of balloon angioplasty on electrocardiography in patients with CTEPH. Methods We evaluated electrocardiograms in 19 patients (mean age, 64±10 years) who underwent balloon pulmonary angioplasty. Results We compared the hemodynamic parameters after balloon pulmonary angioplasty. The mean pulmonary artery pressure was decreased (p<0.001), and the cardiac index was increased (p=0.025) after balloon pulmonary angioplasty. The level of brain natriuretic peptide was decreased (p=0.001) after balloon pulmonary angioplasty (p<0.001). We applied 15 criteria for right ventricular hypertrophy to the patients, according to the American Heart Association recommendations of the electrocardiogram, after balloon pulmonary angioplasty. Among the criteria, the numbers of patients who met the criteria of deep S in V6 (p=0.005) and max R in V1, 2+max S in I, aVL-S in V1 (p=0.046) were significantly decreased after balloon pulmonary angioplasty. The mean numbers regarding the right ventricular hypertrophic criteria in each patient were significantly decreased after balloon pulmonary angioplasty (4.8±2.6 to 3.1±2.5, p=0.003). Conclusion In addition to improvement in hemodynamics, improvement in right ventricular hypertrophy was also observed using the electrocardiographic criteria in patients with CTEPH after balloon pulmonary angioplasty, suggesting that we should pay more attention to these changes.


Assuntos
Angioplastia com Balão/efeitos adversos , Eletrocardiografia/métodos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/cirurgia , Hipertrofia Ventricular Direita/fisiopatologia , Embolia Pulmonar/complicações , Embolia Pulmonar/cirurgia , Idoso , Feminino , Hemodinâmica/fisiologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade
19.
Biol Pharm Bull ; 42(4): 531-537, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30930412

RESUMO

DNA suffers various types of damage even in a normal condition, although they are rapidly repaired by mechanisms called DNA repair. Most progeroid syndromes are caused by genetic defects in specific molecules involved in the DNA repair. DNA damage activates a broad range of signaling pathway that leads to repair, cell cycle arrest, apoptosis and so on, which is called DNA damage response. Recent studies revealed that persistent DNA damage response triggers induction of cell senescence and senescence-associated secretory phenotype (SASP). Here, we review recent advances in the understanding of the molecular mechanisms by which SASP components are regulated, and discuss the possible roles of DNA damage and the DNA damage response, and SASP in the pathogenesis of cardiovascular disease.


Assuntos
Doenças Cardiovasculares , Senescência Celular , Dano ao DNA , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Instabilidade Genômica , Humanos , Inflamação/genética , Inflamação/patologia
20.
Mol Clin Oncol ; 10(1): 37-42, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30655975

RESUMO

Although the use of trastuzumab has been reported to improve overall survival in patients with HER2-positive breast cancer, there is increasing concern about the adverse effects of trastuzumab-induced cardiotoxicity (TIC). The aim of the present study was to investigate the predictor of TIC and to consider appropriate management for such patients. The present study breast cancer 119 patients with breast cancer who had been treated with trastuzumab. Patients were referred to our department for cardiac function screening. The patients' baseline characteristics, echocardiographic data, presence of trastuzumab-induced cardiotoxicity (TIC) and all-cause mortality were investigated. TIC was defined as a manifestation of overt heart failure or ≥10% reduction of left ventricular ejection fraction (LVEF) from baseline to an LVEF <55% in asymptomatic patients. During the follow-up period (mean, 1,410 days), symptomatic heart failure occurred in 2 out of 119 patients (1.6%), 11 patients (9.2%) had asymptomatic impairment of cardiac function that was ameliorated by discontinuing trastuzumab and 20 patients (16.8%) succumbed to cancer-associated fatality. In the logistic regression analysis, only the presence of valvular heart disease at the baseline was indicated to be a predictor of TIC. There was no other predictor for TIC, including baseline characteristics, other therapies and echocardiographic parameters. In addition, impairment of cardiac function was ameliorated by discontinuing trastuzumab. TIC occurred in ~10% of the patients treated with trastuzumab. Only the presence of valvular heart disease seems to be associated with occurrence of TIC, with no other specific predictor of TIC demonstrated in the present study. The present data suggests the importance of regular monitoring of cardiac function, and that presence of valvular heart disease may be a possible predictor of TIC.

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